Vac­cine against sweet itch shows prom­ise

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Swiss re­searchers are de­vel­op­ing a vac­cine to re­duce the sever­ity of in­sect bite hy­per­sen­si­tiv­ity (IBH)--an itchy and per­sis­tent im­mune re­ac­tion to bites of cer­tain tiny gnats that oc­curs in some horses.

The vac­cine tar­gets in­ter­leukin 5 (IL-5), a sub­stance pro­duced by the horse’s im­mune sys­tem. “IL-5 is the mas­ter-reg­u­la­tor of white blood cells called eosinophil­s,” ex­plains An­to­nia Fet­telschoss-Gabriel, PhD, of the Uni­ver­sity Hos­pi­tal Zurich. “Eosinophil­s are well known to play a role in al­ler­gic re­ac­tions. Th­ese cells con­tain large gran­ules with toxic en­zymes that, once re­leased, are ca­pa­ble of caus­ing mas­sive tis­sue de­struc­tion.”

When a horse with IBH is bit­ten by a Culi­coides midge, the in­sect’s saliva trig­gers an im­mune re­ac­tion that leads to eosinophil in­fil­tra­tion into the skin. “Eosinophil­s be­come ac­ti­vated and re­lease their cell con­tent due to the un­der­ly­ing al­ler­gic im­mune re­sponse, which in turn causes tis­sue dam­age of the skin and leads to the typ­i­cal IBH le­sions,” says Fet­telschoss-Gabriel. IBH causes in­tense itch­i­ness so horses of­ten rub raw the af­fected ar­eas---typ­i­cally their mid­line, chests, crests and top of the tail.

The vac­cine works by trick­ing the body into iden­ti­fy­ing IL-5 as a for­eign in­vader to be neu­tral­ized. To ac­com­plish this, re­searchers at­tached IL-5 to a pro­tein from an un­re­lated virus. “Th­ese [pro­teins] are for­eign to the horse’s im­mune sys­tem, so they are able to ef­fi­ciently ac­ti­vate it … and pro­duce an­ti­bod­ies against self,” says Fet­telschoss-Gabriel. “This is a well-known phe­nom­e­non in im­munol­ogy called hap­ten­car­rier com­plex.”

To test the vac­cine, the re­searchers se­lected 34 healthy Ice­landic Horses, a breed known to be sus­cep­ti­ble to IBH. Nine­teen horses were given a se­ries of IBH vac­ci­na­tions: one at the start of the study, and then four, eight, 12 and 20 weeks later. The re­main­ing 15 horses re­ceived sham vac­cines on the same sched­ule to serve as con­trols.

Ini­tially, the re­searchers

found that all but two of the vac­ci­nated horses had de­vel­oped an­ti­bod­ies to IL-5. Over the course of a year, eight of the vac­ci­nated horses (47 per­cent) showed a 50 per­cent re­duc­tion in clin­i­cal signs of IBH, such as itch­ing and skin ir­ri­ta­tion, and four of the vac­ci­nated horses (21 per­cent) had a 75 per­cent drop in IBH signs. Dur­ing the same time pe­riod, only two (13 per­cent) horses in the con­trol group im­proved by 50 per­cent and none showed a 75 per­cent re­duc­tion in IBH signs.

The goal of the vac­cine is to con­trol but not elim­i­nate eosinophil ac­tion in IBH, be­cause the cells per­form other es­sen­tial func­tions, ex­plains Fet­telschoss-Gabriel: “A basal level of eosinophil­s re­mained---the vac­cine did not com­pletely abol­ish eosinophil pro­duc­tion.”

Eosinophil­s sup­port im­mune re­sponses against par­a­sites, so the re­searchers de­ter­mined the par­a­site bur­den in the study horses be­fore and after re­ceiv­ing the vac­cine to see whether that func­tion was af­fected.

“We did not see an in­crease [in in­ter­nal par­a­sites] in vac­ci­nated horses when com­pared to placebo horses. Mean­while, we have horses treated with this vac­cine for three years and have not found a pos­i­tive cor­re­la­tion with par­a­site bur­den,” says Fet­telschoss-Gabriel, adding that while this study was based on Ice­landic Horses, sub­se­quent clin­i­cal tri­als us­ing horses of other breeds pro­duced sim­i­lar re­sults. She says reg­u­la­tory stud­ies must still be done be­fore the IBH vac­cine can be brought to the mar­ket; she es­ti­mates that it may be avail­able by 2021.

Ref­er­ence: “Treat­ing in­sect­bite hy­per­sen­si­tiv­ity in horses with ac­tive vac­ci­na­tion against IL-5,” Jour­nal of Al­lergy and Clin­i­cal Im­munol­ogy, April 2018

When a horse with in­sect bite hy­per­sen­si­tiv­ity is bit­ten by a midge, the in­sect’s saliva trig­gers an im­mune re­ac­tion that leads to eosinophil in­fil­tra­tion into the skin.

Culi­coides midge

eosinophil sweet itch

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